Fabien Hyafil1,2, Jaroslav Pelisek3, Iina Laitinen4, Margret Schottelius5, Miriam Mohring4, Yvonne Döring6, Emiel P C van der Vorst6, Michael Kallmayer3, Katja Steiger7, Andreas Poschenrieder5, Johannes Notni5, Johannes Fischer8, Christine Baumgartner8, Christoph Rischpler4,2,3,5,6,7,8,9, Stephan G Nekolla4,2,3,5,6,7,8,9, Christian Weber6,7,8,9,10, Hans-Henning Eckstein3, Hans-Jürgen Wester5, Markus Schwaiger4,2,3,5,6,7,8,9. 1. Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany fabien.hyafil@gmail.com. 2. Department of Nuclear Medicine, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, Inserm 1148, DHU FIRE, University Diderot, Paris, France. 3. Department of Vascular and Endovascular Surgery, Klinikum Rechts der Isar, Munich, Germany. 4. Department of Nuclear Medicine, Klinikum Rechts der Isar, Munich, Germany. 5. Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany. 6. Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany. 7. Institute of Pathology, Technische Universität München, Munich, Germany. 8. Centre of Preclinical Research, Klinikum Rechts der Isar, Munich, Germany. 9. DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.) partner site Munich Heart Alliance, Munich, Germany; and. 10. Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Abstract
68Ga-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of 68Ga-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of 125I-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of 68Ga-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively; P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced 125I-pentixafor uptake in atherosclerotic plaques by approximately 40%. 125I-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r2 = 0.61; P < 0.05). Conclusion: 68Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to 18F-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.
68Ga-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods:Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of 68Ga-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of 125I-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of 68Ga-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively; P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced 125I-pentixafor uptake in atherosclerotic plaques by approximately 40%. 125I-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r2 = 0.61; P < 0.05). Conclusion:68Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a potential alternative to 18F-FDG for the assessment of macrophage infiltration in atherosclerotic plaques.
Authors: Heather L Teague; Mark A Ahlman; Abass Alavi; Denisa D Wagner; Andrew H Lichtman; Matthias Nahrendorf; Filip K Swirski; Frank Nestle; Joel M Gelfand; Mariana J Kaplan; Steven Grinspoon; Paul M Ridker; David E Newby; Ahmed Tawakol; Zahi A Fayad; Nehal N Mehta Journal: J Am Coll Cardiol Date: 2017-09-12 Impact factor: 24.094
Authors: Nicholas R Evans; Jason M Tarkin; Elizabeth Pv Le; Rouchelle S Sriranjan; Andrej Corovic; Elizabeth A Warburton; James Hf Rudd Journal: Br J Radiol Date: 2020-04-03 Impact factor: 3.039